HHV-6.’ Even if the attack rate of 60% is overestimated by diagnostic error, we can estimate that at least 50% (60 x 0-8 50) of Japanese infants are attacked by ES. This attack rate of ES in Japan is much higher than that in the USA. Different endemicity of HHV-6 and/or difference ofimmunogenetic backgrounds between Japan and western countries may be the explanation.




Department of Pediatrics, Faculty of Medicine, Kyushu Unniversity, Fukuoka 812, Japan

Recording from 10-week-old infant. Traces show arterial oxygen saturation (Sa02), light plethysmographic waveforms from pulse oximeters, breathing movements from volumatic and transcutaneous capsule (Graseby), P02 (Kontron), electroencephalogram (ECG) Arrow marks where oximeter with incorrectly applied oxysensor was disconnected, and appropriately applied sensor was reconnected to recorder.

A close examination of the sensor reading Sa02 80-82 % revealed that a proportion of the emitted light was "shunting" past the tissue bed directly onto the receiving diodes. On readjustment of the position of this sensor, values of between 97-100% were obtained. In clinical practice such discrepancies could lead to the excessive administration of additional inspired oxygen, which in the preterm infant, could result in an increased risk of retinopathy and other possible manifestations of oxygen toxicity. Our observation illustrates the importance of in-service training in the use of pulse oximetry, as well as regular checking by nursing and medical staff of sensor application, including that fresh adhesive is used in securing the sensor on the patient to avoid the possibility of slippage after prolonged monitoring. Ideally, pulse oximeters should be able to identify this abnormal light transmission to the user. Academic Department of Paediatrics, North Staffordshire Hospital Centre, Stoke-on-Trent ST4 6QG, UK


1. Bucher HU, Fanconi S, Baeckert P, Duc G. Hyperoxemia in newborn infants: detection by pulse oximetry. Pediatrics 1989; 84: 226-30. 2. Southall DP, Bignall S, Stebbens VA, Alexander JR, Rivers R, Lissauer T. Pulse oximeter and transcutaneous arterial oxygen measurements in neonatal and paediatric intensive care. Arch Dis Child 1987; 62: 882-88. 3. Poets CF, Stebbens VA, Alexander JR, Arrowsmith WA, Salfield SAW, Southall DP. Arterial oxygen saturation in preterm infants at discharge from hospital and six weeks later. J Pediatrics 1992; 120: 447-54. 4. Stebbens VA, Poets CF, Alexander JA, Arrowsmith WA, Southall DP. Oxygen saturations and breathing patterns in infancy I: fullterm infants in the second month of life. Arch Dis Child 1991; 569: 573.

Attack rate of exanthem subitum in


SIR,-Exanthem subitum (ES) is a common exanthematous early infancy and is a manifestation of human

disease in

herpesvirus-6 (HHV-6) infection.1,2 About 30% of all infants develop apparent ES in western countriesWe have the impression that Japanese infants are more affected by ES than infants in the west. However, the attack rate of ES among infants in Japan is unknown. We sent a questionnaire in January, 1991, to 76 paediatricians about history of ES in their children older than 12 months of age. All these paediatricians were trainees on the paediatric wards of our university hospital and its affiliated hospitals between 1975 and 1986. Our diagnostic criteria for ES were age less than 3 years, preceding fever of 2 or 4 days’ duration, and appearance of pink maculopapular rash mainly on trunk and coincident with abatement of fever. Replies on 115 children (57 male and 58 female) from 56 paediatricians (74%) were obtained. Among these 115 children, 70 (61%) had a history of ES. No difference was observed between males (61 %) and females (60%). The ages of onset of E S ranged from 2 to 21 months, and peaked at 6 months. In our serological study, in 81 % of patients, clinical ES was due

1. Yamanishi K, Okuno T, Shiraki K, et al. Identification of human herpesvirus-6 as a causal agent for exanthem subitum. Lancet 1988; i: 1065-67. 2. Ueda K, Kusuhara K, Hirose M, et al. Exanthem subitum and antibody to human herpesvirus-6. J Infect Dis 1989; 159: 750-52. 3. Krugman S, Katz SL, Gershon AA, et al. Infectious diseases of children. 9th ed. St Louis: Mosby, 1992: 377-80. 4. Ueda K, Miyazaki C, Okada K, et al. Human herpesvirus-6 (HHV-6): clinical and epidemiologic aspects on exanthema subitum. First International Herpesvirus Symposium in Japan, June 23-24, 1992: 19 (abstr).

Intrauterine transmission of human

herpesvirus 6 SIR,-Primary infection with human herpesvirus 6 (HHV-6) is the cause of exanthem subituml and acute febrile illness without rash2 in young children. Serological studies showed that HHV-6 infection generally occurs early in life, after the disappearance of maternal HHV-6 antibodies.3 Dr Dunne and Dr Demmler’s (July 11, p 121) finding of HHV-6-specific IgM antibody in cord-blood sera suggests the possibility of congenital infection. We provide direct evidence of intrauterine HHV-6 transmission. We have analysed thymus samples from 52 fetuses for the presence of HHV-6 by the polymerase chain reaction (PCR). Fetuses were obtained through induced abortion from HIV-1seropositive women who had decided to interrupt their pregnancy because of HIV infection and had given their informed consent for the study. Fetal organs and body fluids were immediately extracted with special care to avoid any cross contamination and kept frozen at 800C until virological study. Genomic DNA was prepared and PCR was done as previously described4 with two distinct HHV-6 -

primer pairs. HHV-6 specific DNA sequences were detected in one thymus sample only, and were also found in the peripheral blood mononuclear cells (PBMCs), liver, spleen, brain, and cerebrospinal fluid from the same fetus. This fetus was obtained after 26 weeks of gestation and did not have any apparent abnormality. No HIV-1specific DNA sequence was detected in the sample from this fetus by PCR with the primer pairs SK38jSK39,S and P3/P4By contrast, both HIV-1and HHV-6 DNA sequences were present in the PBMCs obtained from the mother at the time of abortion. Restriction patterns of HHV-6-specific amplified products from the fetus were identical to those from the mother and showed that the virus belonged to HHV-6 group IL4 IgG antibody titre to HHV-6 was measured by indirect immunofluorescence assay:’ maternal serum and fetal plasma showed a similar titre of 640, substantially higher than those seen in healthy subjects with the same assay.7 No HHV-6-specific IgM antibody was detected in either sample. The presence of HHV-6 DNA in fetal tissues might have been due to the contamination by maternal blood at the time of abortion and, in this case, the apparent lack of HI V transmission could be due to a low HIV-1 copy number in fetus. To exclude blood contamination, we quantified in parallel PCR runs the amount of HIV-1and HHV-6 DNA sequences in PBMCs from mother and fetus with serial five-fold dilutions of cell DNA. The end-point dilutions of DNA for the detection of HIV-1 and HHV-6 were 4 ng (lane 3, figure) and 0-8 ng (lane 4), respectively, in the mother, and more than 5 ug (lane 7) and less than 1-6 ng (lane 12) in the fetus. Therefore, the ratios of end-point HIV-1-positive dilution to end-point HHV-6-positive dilution were 5 in the mother and greater than 3125 in the fetus. This striking difference could not fit with maternal blood contamination since, in this case, these ratios should be similar.


baseline23 has provided evidence that low dietary magnesium is predictive of IHD. 7-day weighed dietary records were kept by 665 men.4 Prevalent heart disease was identified by the London School of Hygiene and Tropical Medicine questionnaire and by electrocardiography, with standard criteria,5 and men were divided into those with symptomatic heart disease (previous myocardial infarction and/or current angina; 97 men) and those with no relevant symptoms (568 men). Incident heart disease events were identified during the following 5 years. These consisted of deaths certified as due to IHD (ICD 410-414) and non-fatal myocardial infarctions that fulfilled World Health Organisation criteria .6 Mean daily intakes of magnesium were: Quantitative HIV-1 and HHV-6 PCR assays on maternal and fetal PBMC DNA. DNA submitted to PCR was serially five-fold diluted from 100 ng (lane to 0-03 ng (lane 6) for maternal PBMCs and from 5 Jlg (lane 7) to 1 6 pg (lane 12) for fetal PBMCs HIV-1 amplification was done with the primers P3/P46 and HHV-6 PCR with the primers 022/023, the sequences of which are located m the major capstde protein gene (022: 5’-GCG TGA ATC AAA CCT CGC TCG-3’; 023. 5’GCC TTA CTC GGA ATC TAC TGC-3’)." Amplified products were analysed on agarose gel, transferred on nylon membranes, and hybridised with ’P-labelled

No of men

/Vo symptomatic IHD //D at af baseline /)aNe//ne No incident event An IHD event af baseline &ae//ne Sy/npfo/TMf/c //-/0 at No incident event An IHD event

Nosymptomatic Symptomatic IHD


oligomer probes. Our results show that HHV-6 can be transmitted in utero in association with maternal viraemia. The absence of maternal HHV-6 IgM antibodies indicates that transmission can occur even when the mother has previous immunity to the virus, but this remains to be confirmed. Intrauterine transmission strengthens even more the relation of HHV-6 to human cytomegalovirus which is also supported by the comparison of genomic organisation8 and antiviral susceptibility.9

JEAN-THIERRY AUBIN Bactériologie-Virologie, CERVI, Hôpital Pitié-Salpétrière, 75651 Paris, France


Centre d’Hémobiologie Périnatale, Hôpital Saint-Antoine, Paris


Laboratoire d’Embryoilogie Pathologique, et de Cytogénétique, Hôpital Saint-Antoine, Paris


Service de


Laboratoire de

Gynécologie-Obstétrique, Hôpital Boucicaut, Paris

K, Okuno T, Shiraki K, et al. Identification of human herpesvirus-6 as causal agent for exanthem subitum. Lancet 1988; i: 1065-67. 2 Prusksananonda P, Breese Hall C, Insel RA, et al. Primary human herpesvirus 6 infection in young children. N Engl J Med 1992; 32: 1445-50. 3. Ueda K, Kusuhara K, Hirose M, et al. Exanthem subitum and antibody to human herpesvirus-6. J Infect Dis 1989; 159: 750-52. 4 Aubin JT, Collandre H, Candotti D, et al. Several groups among human herpesvirus 6 can be distinguished by southern blotting and polymerase chain reaction. J Clin Microbiol 1991; 29: 367-72 5. Ou CY, Kwok S, Mitchell SW, et al DNA amplification for direct detection of HIV-1 in DNA of peripheral blood mononuclear cells. Science 1988, 239: 295-97. 6 Laure F, Courgnaud V, Rouzioux C, et al. Detection of HIV-1 DNA in infants and children by means of polymerase chain reaction. Lancet 1988; ii: 538-40. 7 Robert C, Agut H, Aubin JT, et al. Detection of antibodies to human herpesvirus 6 using immunofluorescence assay. Res Virol 1990; 141: 545-55. 8 Lawrence GL, Chee M, Craxton MA, Compels UA, Honess RW, Barrell BG. Human herpesvirus 6 is closely related to human cytomegalovirus. J Virol 1990; 64: 287-99. 9. Agut H, Aubin JT, Huraux JM. Homogeneous susceptibility of distinct human herpesvirus 6 to antivirals in vitro. J Infect Dis 1991; 163: 1382-83. 1 Yamanishi

Dietary magnesium and prediction

of heart

disease SIR,-The LIMIT-2 trial (June 27, p 1553) makes a most important contribution to a confused topic-ie, the relevance of magnesium to ischaemic heart disease (IHD). This new evidence establishes the value of magnesium in the treatment of myocardial mfarction. But what is its role in prevention before infarction? Magnesium has long been of interest in relation to IHD. One observation consistent with an aetiological role is reduced amounts in the myocardium of subjects whose deaths had been certified as due to heart disease, even when death had been "sudden". The Caerphilly Heart Disease study of men aged 45-59 years at

540 28 87 10

Mean intake

(SD) (mg Mgjday) 310 310 (105) 274 (81) 283 283 (91) (91)

248 (86)

The mean daily intake of magnesium was about 12 % lower in men who later had an IHD event, both in those with IHD at baseline and those without. Overall, the intake was lower by 38-9 mg (95% confidence interval [CI] 5 3-72mg) in those who had an event, and adjustment for the presence or absence of baseline symptoms reduces this difference to 35-6 mg daily (95% CI 2-0-691).


Epidemiology Unit (South Wales), Llandough Hospital, Penarth, South Glamorgan CF6 1XX, UK


1. Elwood



4. 5.


PC, Sweetnam PM, Beasley WH, Jones D, France R. Magnesium and calcium in the myocardium: cause of death and area differences. Lancet 1980; ii: 720-22. Caerphilly and Speedwell Collaborative Group Caerphilly and Speedwell collaborative heart disease studies. J Epidemiol Community Health 1984; 38: 259-62. The Caerphilly Collaborative Heart Disease Studies. Project description and manual of operations. Cardiff: MRC Epidemiology Unit, 1985. Fehily AM, Yarnell JWG, Butland BK. Diet and ischaemic heart disease in the Caerphilly study. Human Nutr Appl Nutr 1987; 41A: 319-26. Bainton D, Baker IA, Sweetnam PM, Yarnell JWG, Elwood PC. Prevalence of ischaemic heart disease: the Caerphilly and Speedwell Surveys. Br Heart J 1988; 59: 201-06. Yarnell JWG, Baker IA, Sweetnam PM, et al. Fibrinogen, viscosity, and white blood cell count are major risk factors for ischemic heart disease: the Caerphilly and Speedwell Collaborative Heart Disease Studies. Circulation 1991; 83: 836-14.

Striking identity between HIV-1 envelope glycoprotein gp120 and its CD4 receptor SIR,--Oligopeptides, such as the pentapeptides homoregulatory peptide and epidermal pentapeptide,l are involved in many biological processes.1-s Some have been mapped in the HIV-1 envelope.4,5 On the basis of the homology that they share with immunoregulatory molecules such as interleukin-2 receptorbinding domain or a-interferon-p I 5E, they are likely to have a role in the immune dysregulation observed in AIDS.4,5 We have designed software (Automat) to find systematically all peptidic homologies between proteins in a bank and a given protein.5 Scanning the HIV-1 envelope sequences revealed a pentapeptide identity (SLWDQ) with the CD4 molecule at positions 110-114 in the HIV-1envelope and 60-64 in CD4. Exploration of the MIPS data bank revealed the pentapeptide sequence in only one other protein, the aminotransferase A64988. The sequence is perfectly conserved among all HIV-1strains (but is lacking in HIV-2 and simian immunodeficiency virus) and in human and chimpanzee CD4. The SLWDQ pentapeptide is located in the N-terminal part of the gpl20 external membrane protein of HIV-1. This segment lies on an accessible loop of the first domain of CD4,6 and is the epitope for the OKT4a monoclonal antibody.’ Moreover this region has an important function in the CD4 molecule since OKT4a monoclonal antibodies (specifically directed towards this region) can block T4 cell immune activation,8 and a W-to-C mutation suppresses the binding of HIV-1.’ In agreement with the above mentioned biological characteristics, the

Intrauterine transmission of human herpesvirus 6.

482 HHV-6.’ Even if the attack rate of 60% is overestimated by diagnostic error, we can estimate that at least 50% (60 x 0-8 50) of Japanese infants...
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